2,5-二甲基-3,4-二乙酰基-1-芳基吡咯的合成

多取代吡咯;二乙酰基己二酮;取代苯胺;2;5-二甲基-3;4-二乙酰基-1-芳基吡咯的合成     

多取代吡咯的合成及其性质(Ⅱ)

前文已报导1-芳基-2-甲基-3-乙酰基-5-对氯苯基吡咯。本文用间硝基-ω-溴代苯乙酮与乙酰丙酮作用,得到1-间硝基苯基-3-乙酰基-1,4-戊二酮(1),(1)与各种不同的芳香族伯胺在冰醋酸存在下进行环合反应,生成1,2,3,5-四取代吡咯(2)至(10)。后者与氨基脲反应得到相应的缩氨脲。     

3-乙酰基取代吡咯衍生物的合成及其晶体结构

本文通过Knorr合成法制备了四个3-位乙酰基取代的吡咯衍生物:1, 2-二甲基-4-异丙基-5-苯基-3-乙酰基-吡咯(5a); 1, 2, 4-三甲基-5-对甲氧苯基-3-乙酰基-吡咯(5b); 1, 2, 5-三甲基-4-苯基-3-乙酰基-吡咯(5c); 1, 2, 5-三甲基-4-对甲氧苯基-3-乙酰基-吡咯(5d)。通过红外, 质谱, 核磁等方法对其结构进行了表征。测定了其中三个化合物的晶体结构。对这类吡咯环上4或5-位有芳环取代基时化合物的晶体结构特征进行了扼要讨论, 晶体衍射实验结果表明,4, 5-位上的芳环与吡咯环本身处于非共平面结构。     

3-N-乙酰基-2-取代芳基-5-[5'-甲基-异噁唑-3']-Δ3-1,3,4－噁唑啉类化合物的合成

甲基-异噁唑甲酰肼;3-N-乙酰基-2-取代芳基-5-[5'-甲基-异噁唑-3']-Δ3-1;3;4－噁唑啉类化合物的合成     

氨基酸合成方法研究(Ⅸ)——固液相转移催化下1,4-二乙酰基-2,5-哌嗪二酮与醛的缩合反应

研究了在固液相转移催化条件下,1,4-二乙酰基-2,5-哌嗪二酮(2)与醛(3a-n)的缩合反应。合成了14种(Z)-1-乙酰基-3-亚芳基(亚烷基)-2,5-哌嗪二酮(4a-n),并讨论了产物的构型。     

立体选择性合成2-呋喃甲酰基-3-芳基-4-乙氧羰基-5-甲基-反式-2,3-二氢呋喃

溴化呋喃甲酰基甲基三苯鉮1与2-乙酰基-3-芳基丙烯酸乙酯2以碳酸钾为碱，在四氢呋喃中室温反应，可以较好的收率、高立体选择性地生成反-2-呋喃甲酰基-3-芳基-4-乙氧羰基-5-甲基-2,3-二氢呋喃3。产物结构均经波谱予以确定。本文还提出了生成产物的可能机理。     

固体超酸二氧化锆催化合成1-芳基-2-甲基-3-乙酰基-5-间硝基苯基吡咯的研究

1-芳基取代吡咯中有许多具有明显的生理效应.我们曾以1-对氯苯基-3-乙酰基-1,4-戊二酮,1,4-二苯基-2-苯甲酰基-1,4-丁二酮,与各种芳香族伯胺在冰醋酸催化下环合制得了相应的1-芳香多取代吡咯.但用冰醋酸作催化剂时,产品的分离精制常会遇到困难.我们按文献[3]合成的固体超酸二氧化锆用于催化酯化反应,效果良好.本文进一步在固体超酸二氧化锆的催化下将1-间硝基苯基-3-乙酰基-1,4-戊二酮     

几种多取代吡咯的NMR研究(Ⅰ)

本文测定了1-笨基-2-甲基-3-乙酰基-5-对氯苯基吡咯(I)等十个多取代吮咯的¹HNMR谱和其中五个化合物的¹³CNMR谱。归属了共振谱线,证实了各化合物的分子结构。得到了2-甲基-3-乙酰基-5-对氯苯基吡咯基-1在苯衍生物中的经验取代基增量。     

酰氨基硫脲及有关的杂环衍生物的研究 I:1-氰乙酰基-4-芳基氨基硫脲及有关的杂环衍生物的合成

合成了九个1-氰乙酰基-4-芳基氨基硫脲类化合物和四个3-氰甲基-4-芳基-1,2,4-三唑啉与硫酮类化合物和四个2-苯基氨基-5-取代-1,3-噻二唑类化合物.并初步研究了这些化合物的抗结核菌活性和植物生长促进作用.     

腈亚胺的1,3-偶极环加成反应合成螺吡唑-吡咯里嗪类化合物

通过2-芳亚甲基-2,3-二氢-1H-吡里-1-酮与腈亚胺[经苯甲酰氯苯腙(2)与三乙胺反应生成]的1,3-偶极环加成反应,以较高收率合成了一系列的4-芳基-2,5-二苯基-2H,4H-二氢-螺[吡唑-3,2’-吡咯里嗪]-1’(3’H)-酮.采用NMR,IR,质谱和元素分析等多种谱学技术对产物进行了结构表征.     

Synthesis of nucleoside analogs of 1,4-oxathiane, 1,4-dithiane,and 1,4-dioxane

The two regioisomers 6-chloro-9-(1, 4-oxathian-3-yl)-9H-purine ( 5 ) and 6-chloro-9-(1,4-oxathian-2-yl)-9H-purine ( 6 ) were obtained when 3-acetoxy-1,4-oxathiane ( 3 ) was subjected to the acid-catalyzed fusion procedure; compound 3 was prepared by a Pummerer reaction with 1,4-oxathiane 4-oxide ( 2 ). The nucleoside analog 6 could he converted into the adenine derivative 7 and 9-(1,4-oxathian-2-yl)-9H-purine-6(1H)thione ( 8 ). The following nucleoside analogs have also been synthesized: 6-chloro-9-(1,4-dithian-2-yl)-9H-purine ( 13 ), 9-(1,4-dithian-2-yl)adenine ( 14 ), 9-(1,4-dithian-2-yl)-9H-purine-6(1H)thione ( 15 ), and 6-chloro-9-(1,4-dioxan-2-yl)-9H-purine ( 18 ).     

Synthese von Plectranthonen,diterpenoiden Phenanthren-1,4-chinonen

Synthesis of Plectranthons, Diterpenoid Phenanthrene-1,4-diones The following phenanthrene-1,4-diones have been synthesized by using the photocyclization of the corresponding highly substituted stilbenes as the key step: 3-hydroxy-5,7,8-trimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione ( 1 ), (RS)-, (R)-, and (S)-2-[3-hydroxy-5,7,8-trimethyl-1,4-dioxophenanthren-2-yl]-1-methylethyl acetate ( 2 , 31 , and 32 , resp.), 3-hydroxy-7,8-dimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione ( 3 ), 3-hydroxy-7,8,10-tri-methyl-2-(prop-2-enyl)phenanthrene-1,4-dione ( 4 ), 5,7,8-trimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione ( 17 ), and 3-hydroxy-2-methylphenanthrene-1,4-dione ( 42 ). The quinones 1 and 3 proved to be identical with the recently isolated plectranthons A and C. Compounds 2 , 31 , and 32 exhibited the same UV/VIS, IR, ¹H-NMR and mass spectra as natural plectranthon B , but had different melting points. This might be due either to crystal modifications or to diastereoisomerism caused by the helical structure of the phenanthrene-1,4-dione skeleton. The spectral data of synthetic 4 were not compatible with those of natural plectranthon D for which structure 4 had been proposed based mainly on ¹H-NMR arguments concerning the chemical shifts of H? C(9) and H? C(10) in 1–3. Extensive ¹H-NMR investigations have now revealed that the currently stated assignments of the H? C(9)/ H? C(10) AB system have to be reversed for highly substituted phenanthrene-1,4-diones: in the model compounds 2-methylphenanthrene-1,4-dione (41) and 2, H? C(10) resonates al lower field as expected (peri-position), whereas in the highly substituted congeners 1 , 2 , 3 , 31 , and 32 , H? C(9) is shifted paramagnetically, a fact which had lead to the erroneous assignment of structure 4 for natural plectranthon D .     

Mercuric ion-catalyzed hydration of derivatives of 1,4-dichloro-2-butyne. Hydration of 1-aryloxy-4-arylthio-2-butynes, 1,4-bis(arylthio)-2-butynes,and 1,4-bis(arylsulfonyl)-1-butynes

The mercuric ion-catalyzed hydration of 1,4-bis(arylthio)-2-butynes and 1-aryloxy-4-arylthio-2-butynes was studied. The 1,4-bis(arylsulfonyl)-2-butynes afforded 1,4-bis(arylsulfonyl)-2-butanones (7). The 1,4-bis(arylthio)-2-butynes afforded a variety of products in acetic acid among which were: 1,4-bis(arylthiomethyl)vinyl acetate ( 18 ); 1,4-bis(arylthio)-2-butanone ( 15 ); 1-(arylthio)-3-buten-2-one ( 16 ); and 1-(arylthio)-4-acetoxy-2-butanone ( 17 ). Ketone 15 eliminates arylthiol in an acidic medium yielding 16 which undergoes Michael addition of solvent to give 17. Treatment of 7 with base in the presence of a nucleophile (ArSH) analogously leads to elimination of arylsulfinic acid, followed by Michael addition of arylthiol. Hydration of 5 in methanol cleanly gave 1-(arylthio)-4-methoxy-2-butanones ( 19 ). In contrast, 1-aryloxy-4-arylthio-24)utynes afforded chromenes ( 8 ) by intramolecular cyclization. No thiochromenes were formed in any of the examples investigated.     

Synthesis of tricyclic and tetracyclic thieno[3,2-f]-1,4-thiazepines

Treatment of 5-methylthio-2,3-dihydrothieno[3,2-f]-1,4-thiazepine ( 9 ) with acylhydrazines gave 5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepines 10, 11 , and that of 9 with ethyl anthranilate gave 5,6-dihydrothieno[3′,2′:6,7][1,4]thiazepino[5,4-b]quinazolin-8-one ( 14 ). Reaction of 9 with hydrazine hydrate or 4-chlorophenylhydrazine afforded 5-hydrazino compounds 12, 15 , which were subsequently cyclized to ethyl 5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepine-3-carboxylate ( 13 ), 2-(4-chlorophenyl)-5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepin-3(2H)-one ( 16 ) and 2-(4-chlorophenyl)-6,7-dihydro-2H-thieno[3,2-f][1,2,4]triazino[4,3-d][1,4]thiazepine-3,4-dione ( 17 ). New thieno-anellated heterocycles were prepared with the aim of studying their affinity for the benzodiazepine receptors.     

Crystal engineering using anilic acids and dipyridyl compounds through a new supramolecular synthon

The anilic acids, 2,5-dihydroxy-1,4-benzoquinone (1a), 2,5-dibromo-3,6-dihydroxy-1,4-benzoquinone (bromanilic acid; 1b), 2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone (chloranilic acid; 1c), and 2,5-dicyano-3,6-dihydroxy-1,4-benzoquinone (cyananilic acid; 1d), were cocrystallized with rigid organic ligands containing two pyridine rings, 2,4-bipyridine (2a), 4,4'-bipyridine (2b), 1,2-bis(2-pyridyl)ethylene (3a), 1,2-bis(4-pyridyl)ethylene (3b), 2,2'-dipyridylacetylene (4a), 3,3'-dipyridylacetylene (4b), and 4,4'-dipyridylacetylene (4c). Fourteen complexes 5-18 were obtained as single crystals, and their crystal structures were successfully determined by X-ray analysis. All complexes except those with 2a are 1:1 and are composed of an infinite linear or zigzag tape structure, the formation of which is ascribed to intermolecular O-H...N, N(+)-H...O, or N(+)-H...O(-) hydrogen bonds or a combination of these between the anilic acids and the dipyridyl compounds. In the complexes 5 and 6, no infinite tape structure is observed although the molecular units connected by a similar hydrogen-bonding pattern are formed. For the 1:1 complexes, we have found two types of stacking arrangements, segregated stacks (7, 9, 12-15, 18) and alternated ones (8, 10, 11, 16, 17). In the complexes of 1c with the series of dipyridylacetylenes 4 (14, 15, 17), the neutral, dication, and monocaction states are formed depending on the nitrogen positions, which can be attributed to the different basicity of the pyridyl groups.     

Conformationally tailored N-[(2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl)carbonyl]proline templates as molecular tools for the design of peptidomimetics. Design and synthesis of fibrinogen receptor antagonists

The proline peptide bond was shown by 2D proton NMR studies to exist exclusively in the trans conformation in benzyl (2S)-1-[[(2S)-2-methyl-6-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl]-2-pyrrolidinecarboxylate [(S,S)-11], benzyl (2S)-1-[[(2S)-2-methyl-7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl]-2-pyrrolidinecarboxylate [(S,S)-9], and in the corresponding 6-amino and 7-amino carboxylic acids (S,S)-3 and (S,S)-4. On the other hand, the diastereomers (R,S)-11 and (R,S)-9 containing an (R)[2-methyl-6/7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl moiety, and the diastereoisomers (R,S)-3 and (R,S)-4 incorporating an (R)[6/7-amino-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl moiety were found to exist as equilibria of trans(63-83%) and cis(17-37%) isomers. These conformationally defined templates were applied in the construction of RGD mimetics possessing antagonistic activity at the platelet fibrinogen receptor.     

Regioselective intramolecular ring closure of 2-amino-6-bromo-2,6-dideoxyhexono-1,4-lactones to 5- or 6-membered iminuronic acid analogues: synthesis of 1-deoxymannojirimycin and 2,5-dideoxy-2,5-imino-D-glucitol

1-Deoxymannojirimycin (8c) was synthesised from 2-amino-6-bromo-2,6-dideoxy-D-mannono-1,4-lactone (7) by intramolecular direct displacement of the C-6 bromine employing non-aqueous base treatment followed by reduction of the intermediate methyl ester. Likewise, using aqueous base at pH 12, ring closure took place by 5-exo attack on the 5,6-epoxide leading to 2,5-dideoxy-2,5-imino-L-gulonic acid (9b), which was reduced to 2,5-dideoxy-2,5-imino-D-glucitol (9b). The method was further applied to 2-amino-6-bromo-2,6-dideoxy-D-galacto- as well as D-talo-1,4-lactones (14 and 15). However, only the corresponding six-membered ring 1,5-iminuronic acid mimetics, namely (2R,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-galactonic acid, 16) and (2S,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-talonic acid, 17), were obtained. The corresponding enantiomers, L-galacto- as well as L-talo-2-amino-6-bromo-2,6-dideoxy-1,4-lactones ent-14 and ent-15, reacted accordingly to give the D-galacto- and L-altro-1,5-iminuronic acid mimetics, (2S,3S,4R,5S)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-L-galactonic acid, ent-16) and (2R,3S,4R,5S)-3,4,5-trihydroxypipecolic acids (2,6-dideoxy-2,6-imino-L-talonic acid, ent-17), respectively.     

Unsaturated 1,2-amino alcohols and ethers from aziridines and organolithiums

Organolithium-induced ring-opening of aziridines of 2,5-dihydrofuran (5 and 8) and 1,4-dimethoxybut-2-ene (16, 17 and 23) gives 3-substituted 2-aminobut-3-en-1-ols 9-15 and amino ethers 18-20 and 24-26.     

Benzolactams. 4. Reaction of 3',4'- or 4',5'-dialkoxy-substituted 1-(2'-Bromobenzyl)-2-ethoxycarbonyl-1,2,3,4-tetrahydroisoquinolines with alkyllithium. 1,2 and 1,4 additions of alkyllithium to benzolactams

Treatment of 1-(2'-bromo-3',4'-dialkoxybenzyl)-1,2,3, 4-tetrahydroisoquinoline carbamates, 1a,c, with excess alkyllithium gave 8-oxoberbines, 2a,c, which were successively attacked in situ with another molecule of alkyllithium to give 1,2 and/or 1,4 addition products. A primary alkyllithium, such as MeLi or BuLi, gave a 1,2 addition product, 8-methyleneberbine 9a or 8-butylideneberbine 3a. t-BuLi preferred 1,4 addition, followed by elimination of the alkoxy group, to give 9-tert-butyl-8-oxoberbine 6a or 7c. s-BuLi gave a mixture of 1,2 and 1,4 addition products, 1-[2'-(2' '-methylbutyryl)benzyl]-1,2,3,4-tetrahydroisoquinoline 4a and 9-s-butyl-8-oxoberbine 5a. Similar treatments of carbamate 1b having no alkoxy group at its 3' position gave 1,2 addition products, 8-butylideneberbine 3b, 1-[2'-(2' '-methylbutyryl)benzyl]-1,2,3, 4-tetrahydroisoquinoline 4b, and 1-(2'-pivaloylbenzyl)-1,2,3, 4-tetrahydroisoquinoline 6b, in all cases. Reactions of 1a with s-BuMgCl and isoPrMgCl also gave the 1,4 adduct, 5a, and its 9-isoPr analogue, 12a. Treatment of 9a with excess NaBH(4) in AcOH gave (+/-)-coralydine (10b).     

Studies on topical antiinflammatory agents. IV. 21-(Alkylthio)acetates and (methylthio)methoxides of corticosteroids

A series of 21-(alkylthio)acetates and 21-(methylthio)methoxides of corticosteroids were synthesized and examined for vasoconstrictive activities. The activities of seven compounds were equal to or greater than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV). Among them, betamethasone 21-(methylthio)acetate 17-propanoate (2Ca) was found to have the most potent activity, which is superior to that of BV. A structure-activity relationship study revealed that substitution of the 21-hydroxy group of corticosteroids with the (methylthio)acetate function is a useful approach for obtaining potent activity.